Modelling the Impact of Interventions Targeting High- Risk Populations on the HCV Epidemic in Resource- Limited Settings Pakistan as a Case Study

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1 1 Modelling the Impact of Interventions Targeting High- Risk Populations on the HCV Epidemic in Resource- Limited Settings Pakistan as a Case Study Aaron G. Lim, Matthew Hickman, Peter Vickerman Population Health Sciences, Bristol Medical School, University of Bristol 24 October 2017

2 2 Ø None. Conflicts of Interest

3 HCV Epidemic in Pakistan 3

4 4 The Global HCV Epidemic is Concentrated Figure: In terms of numbers, Pakistan has the world s second- largest HCV burden. Gower et al. J Hep (2014) Global Hepatitis Report 2017

5 5 The Global HCV Epidemic is Concentrated Estimated 71 million chronic HCV infections globally in 2015 Ø Pakistan: ~7.5 million infections Ø >10% of global HCV burden Figure: Updated global HCV estimates put Pakistan s HCV epidemic into perspective. Gower et al. J Hep (2014) Global Hepatitis Report 2017

6 6 Characterising the HCV Epidemic in Pakistan Ø Large, rapidly growing population ~197 million in 2017 è ~ million by 2030

7 7 Characterising the HCV Epidemic in Pakistan Ø Large, rapidly growing population ~197 million in 2017 è ~ million by 2030 Ø High chronic HCV prevalence which is increasing 3.6% overall (2007 National Survey data 1 ) ~ % per decade (blood donor data) 1 Qureshi et al. EMHJ (2010)

8 8 Characterising the HCV Epidemic in Pakistan Ø Large, rapidly growing population ~197 million in 2017 è ~ million by 2030 Ø High chronic HCV prevalence which is increasing 3.6% overall (2007 National Survey data 1 ) ~ % per decade (blood donor data) Ø Risk factors for transmission of HCV 1,2 Injecting drug use: ~430,000 in 2012, 62% Chronic Prev 3-4 Medical risk: e.g. blood transfusions, surgery, haemodialysis, medical injections Community risk: e.g. barbering, ear/nose piercing, tattooing, acupuncture 1 Qureshi et al. EMHJ (2010), 2 Trickey et al., AJTMH (2017), 3 UNODC Drug Use in Pakistan Report 2013, 4 Nelson et al., Lancet (2011)

9 9 Characterising the HCV Epidemic in Pakistan Ø Large, rapidly growing population ~197 million in 2017 è ~ million by 2030 Ø High chronic HCV prevalence which is increasing 3.6% overall (2007 National Survey data 1 ) ~ % per decade (blood donor data) Ø Risk factors for transmission of HCV 1,2 Injecting drug use: ~430,000 in 2012, 62% Chronic Prev 3-4 Medical risk: e.g. blood transfusions, surgery, haemodialysis, medical injections Community risk: e.g. barbering, ear/nose piercing, tattooing, acupuncture Ø Historical treatment with non- DAAs from * ~1-2% of chronic infections each year (public sector data) Treatment level as of the end of 2015 was 150,000/yr 1 Qureshi et al. EMHJ (2010), 2 Trickey et al., AJTMH (2017), 3 UNODC Drug Use in Pakistan Report 2013, 4 Nelson et al., Lancet (2011), *Commensurate 40/60 scale- up in private sector

10 10 Determining The Way Forward Objectives 1 Project the likely trajectory of the HCV epidemic in Pakistan

11 11 Determining The Way Forward Objectives 1 Project the likely trajectory of the HCV epidemic in Pakistan 2 Identify the impact of prevention and treatment interventions, especially those targeting high- risk persons, e.g. people who inject drugs (PWID)

12 12 Methods Ø Stratified general population dynamic transmission model based on an Susceptible- Infected- Treatment (S- I- T) framework Demographics (age, gender, population growth) People who inject drugs (PWID) Low and high medical + community risk HCV transmission Disease progression (pre- cirrhosis, cirrhosis, decompensation, HCC)

13 13 Methods Ø Stratified general population dynamic transmission model based on an Susceptible- Infected- Treatment (S- I- T) framework Demographics (age, gender, population growth) People who inject drugs (PWID) Low and high medical + community risk HCV transmission Disease progression (pre- cirrhosis, cirrhosis, decompensation, HCC) Ø Calibrate the model to Pakistan- specific data Ø Focus mainly on what has been happening since 2016 At baseline, assume no interventions from 2016

14 1 Epidemic Projections 14

15 15 Overall Chronic HCV Prevalence (%) Chronic HCV Prevalence Year 1 Figure: Model projections suggest ~3.9% chronic HCV prevalence in 2016 (7.5 million Qureshi et al. EMHJ (2010) chronic prevalent infections), increasing to ~5.1% (12.6 million) by Lim et al., Under Review

16 16 Overall Chronic HCV Prevalence (%) Chronic HCV Prevalence In 2016: Ø PWID prevalence: ~0.29% of total pop Ø HCV in PWID: ~4.5% of ALL chronic infections Year 1 Figure: Model projections suggest ~3.9% chronic HCV prevalence in 2016 (7.5 million Qureshi et al. EMHJ (2010) chronic prevalent infections), increasing to ~5.1% (12.6 million) by Lim et al., Under Review

17 17 Total HCV Incidence (per 1000 pyrs) HCV Incidence is Continuing to Rise Year 1 Figure: HCV incidence is also projected to increase: 700,000 new infections in 2016, up Qureshi et al. EMHJ (2010) to 1.1 million new infections in Lim et al., Under Review

18 18 Total HCV Incidence (per 1000 pyrs) Year Figure: A disproportionate number of new infections will be attributable to PWID. Lim et al., Under Review 1 Qureshi et al. EMHJ (2010) HCV Incidence is Continuing to Rise Between : Ø ~14% of new infections due to PWID-related transmission

19 2 Impact of Interventions 19

20 20 Illustrative Intervention Scenarios Ø Reducing HCV incidence is crucial to controlling the epidemic

21 21 Illustrative Intervention Scenarios Ø Reducing HCV incidence is crucial to controlling the epidemic Ø Consider the following intervention scenarios from 2017: No treatment & halve PWID- related HCV transmission Treat 150,000 treatments/yr ( Status Quo ) with DAAs Treat 150,000 treatments/yr targeting 40% of PWID Treat 300,000 patients/year with no targeting Treat 300,000 patients/year targeting 40% of PWID Treat 300,000 patients/year targeting 40% of PWID and halving PWID transmission

22 22 Illustrative Intervention Scenarios Ø Reducing HCV incidence is crucial to controlling the epidemic Ø Consider the following intervention scenarios from 2017: No treatment & halve PWID- related HCV transmission Treat 150,000 treatments/yr ( Status Quo ) with DAAs Treat 150,000 treatments/yr targeting 40% of PWID Treat 300,000 patients/year with no targeting Treat 300,000 patients/year targeting 40% of PWID Treat 300,000 patients/year targeting 40% of PWID and halving PWID transmission

23 23 Illustrative Intervention Scenarios Ø Reducing HCV incidence is crucial to controlling the epidemic Ø Consider the following intervention scenarios from 2017: No treatment & halve PWID- related HCV transmission Treat 150,000 treatments/yr ( Status Quo ) with DAAs Treat 150,000 treatments/yr targeting 40% of PWID Treat 300,000 patients/year with no targeting Treat 300,000 patients/year targeting 40% of PWID Treat 300,000 patients/year targeting 40% of PWID and halving PWID transmission

24 24 Illustrative Intervention Scenarios Ø Reducing HCV incidence is crucial to controlling the epidemic Ø Consider the following intervention scenarios from 2017: No treatment & halve PWID- related HCV transmission Treat 150,000 treatments/yr ( Status Quo ) with DAAs Treat 150,000 treatments/yr targeting 40% of PWID Treat 300,000 patients/year with no targeting Treat 300,000 patients/year targeting 40% of PWID Treat 300,000 patients/year targeting 40% of PWID and halving PWID transmission

25 25 Illustrative Intervention Scenarios Ø Reducing HCV incidence is crucial to controlling the epidemic Ø Consider the following intervention scenarios from 2017: No treatment & halve PWID- related HCV transmission Treat 150,000 treatments/yr ( Status Quo ) with DAAs Treat 150,000 treatments/yr targeting 40% of PWID Treat 300,000 patients/year with no targeting Treat 300,000 patients/year targeting 40% of PWID Treat 300,000 patients/year targeting 40% of PWID and halving PWID transmission

26 Without Intervention From Without Intervention From 2016 No Treat & Halve PWID Trans. Treat 150,000/Yr Non-Targeted Treat 150,000/Yr Target PWID Treat 300,000/Yr Non-Targeted Treat 300,000/Yr Target PWID Treat 300,000/Yr Target PWID & Halve PWID Trans. Ø ~1.1 million new infections in 2030 Total HCV Incidence (per 1000 pyrs) Intervention Start Year

27 Without Intervention From 2016 No Treat & Halve PWID Trans. Treat 150,000/Yr Non-Targeted Treat 150,000/Yr Target PWID Treat 300,000/Yr Non-Targeted Treat 300,000/Yr Target PWID Treat 300,000/Yr Target PWID & Halve PWID Trans. No Treatment Halve PWID Transmission Only Total HCV Incidence (per 1000 pyrs) Ø Averts 860,000 2 new infections over 15 years 1 Ø Minimal reduction in incidence Ø Treatment is needed to reduce prevalent infections Intervention Start Year 27

28 28 Status Quo : Treat 150,000/Yr With DAA Without Intervention From 2016 No Treat & Halve PWID Trans. Treat 150,000/Yr Non-Targeted Treat 150,000/Yr Target PWID Treat 300,000/Yr Non-Targeted Treat 300,000/Yr Target PWID Treat 300,000/Yr Target PWID & Halve PWID Trans. Ø Non-targeted and targeted treatment similar reductions in incidence Ø Incidence rate is nearly stabilised Total HCV Incidence (per 1000 pyrs) Intervention Start Year

29 Treat 300,000/Yr Non-Targeted Vs. Targeting PWID 29 Without Intervention From 2016 No Treat & Halve PWID Trans. Treat 150,000/Yr Non-Targeted Treat 150,000/Yr Target PWID Treat 300,000/Yr Non-Targeted Treat 300,000/Yr Target PWID Treat 300,000/Yr Target PWID & Halve PWID Trans. Ø Targeting treatment to PWID has greater impact after treatment scale-up Total HCV Incidence (per 1000 pyrs) Intervention Start Year

30 Without Intervention From 2016 No Treat & Halve PWID Trans. Treat 150,000/Yr Non-Targeted Treat 150,000/Yr Target PWID Treat 300,000/Yr Non-Targeted Treat 300,000/Yr Target PWID Treat 300,000/Yr Target PWID & Halve PWID Trans. Ø Combining treatment with prevention of HCV transmission is crucial to halting the epidemic Treat 300,000/Yr, Target 40% of PWID 30 & Halve PWID Transmission Total HCV Incidence (per 1000 pyrs) Intervention Start Year

31 31 TasP & Treatment Efficacy Ø Treatment- as- Prevention (TasP): Targeting treatment to those with high risk of transmission can lead to onward prevention benefits Treatment coverage must be sufficiently high Ø Treatment efficacy: E.g. # of new infections averted per treatment over the time period Larger is better

32 Infections Averted Per 1000 Treatments # of Infections Averted Per 1000 Treatments Number of Infections Averted Per 1000 Treatments Treat 150,000/Yr Non-Targeted Treat 150,000/Yr Target PWID Treat 300,000/Yr Non-Targeted Treat 300,000/Yr Target PWID Treat 300,000/Yr Target PWID & Halve PWID Transmission By Year End

33 Infections Averted Per 1000 Treatments # of Infections Averted Per 1000 Treatments Re-Infection Risk is High if Treatment is Insufficient Treat 150,000/Yr Non-Targeted Treat 150,000/Yr Target PWID Treat 300,000/Yr Non-Targeted Treat 300,000/Yr Target PWID Treat 300,000/Yr Target PWID & Halve PWID Transmission Between : Ø 560 IA/1000Trt Ø 540 IA/1000Trt By Year End

34 Infections Averted Per 1000 Treatments # of Infections Averted Per 1000 Treatments Targeting + More Treatment Accumulates Prevention Benefit Treat 150,000/Yr Non-Targeted Treat 150,000/Yr Target PWID Treat 300,000/Yr Non-Targeted Treat 300,000/Yr Target PWID Treat 300,000/Yr Target PWID & Halve PWID Transmission Between : Ø 570 IA/1000Trt Ø 610 IA/1000Trt By Year End

35 Infections Averted Per 1000 Treatments # of Infections Averted Per 1000 Treatments Combining Treatment Scale-Up & Risk Reduction Treat 150,000/Yr Non-Targeted Treat 150,000/Yr Target PWID Treat 300,000/Yr Non-Targeted Treat 300,000/Yr Target PWID Treat 300,000/Yr Target PWID & Halve PWID Transmission Between : Ø 880 IA/1000Trt By Year End

36 Conclusions 36

37 37 Conclusions: Model Projections 1 The burden of HCV infection in Pakistan is likely to increase markedly in the near future Current levels of intervention are not enough to reduce the general HCV epidemic in Pakistan, even with new DAA treatments

38 38 Conclusions: Model Projections 1 The burden of HCV infection in Pakistan is likely to increase markedly in the near future Current levels of intervention are not enough to reduce the general HCV epidemic in Pakistan, even with new DAA treatments 2 Combining prevention & treatment has the greatest impact Risk reduction can prevent onward transmission, but alone is not enough to reduce the epidemic treatment is needed High- coverage, targeted treatment to high- risk populations, such as PWID, can avert a greater number of new infections per treatment

39 39 Conclusions: Model Projections 1 The burden of HCV infection in Pakistan is likely to increase markedly in the near future Current levels of intervention are not enough to reduce the general HCV epidemic in Pakistan, even with new DAA treatments 2 Combining prevention & treatment has the greatest impact Risk reduction can prevent onward transmission, but alone is not enough to reduce the epidemic treatment is needed High- coverage, targeted treatment to high- risk populations, such as PWID, can avert a greater number of new infections per treatment Even in general population HCV epidemics, as in Pakistan, such targeted treatment & prevention scale- up can play an important role in curbing the overall HCV burden

Martin (UoB; UC San Diego) Pakistan Hepatitis Prevention and Control Team: Huma Qureshi (PHRC) Francisco

40 Thank you! 40 Acknowledgements University of Bristol: Peter Vickerman Josephine G. Walker Charlotte F. Davies Adam Trickey Hannah Fraser Christinah Mukandavire Matthew Hickman Margaret May Natasha K. Martin (UoB; UC San Diego) Pakistan Hepatitis Prevention and Control Team: Huma Qureshi (PHRC) Francisco Averho (DVH- CDC) Nancy Glass (DVH- CDC) Hassan Mahmood (TEPHINET- CDC) Saeed Hamid (AKU) Quaid Saeed (National AIDS Control Programme)

41 41

42 Additional Slides 42

43 Global HCV Epidemic & WHO Targets 43

44 44 What is HCV? Ø Hepatitis C virus (HCV) is a blood- borne virus Can cause acute and chronic hepatitis C affecting the liver Ø Globally, estimated 71 million chronic (viraemic) infections in 2015 ~1% of world s population Ø Approx. 700,000 HCV- related deaths annually Cirrhosis, decompensation, and hepatocellular carcinoma Ø Epidemic is concentrated in few countries Low- middle income countries (LMIC) account for 80% of chronic infections and mortality Ø There is a cure treatment achieves sustained virologic response (SVR) Conventional IFN- based treatment (e.g. IFN+RBV), SVR ~50% From 2014, direct- acting antivirals (DAAs), up to ~90-95% SVR Global Hepatitis Report 2017 Gower et al., J Hep (2014) Graham and Swan, Antiviral Res (2015)

45 45 WHO Targets for HCV Elimination by 2030 Figure: Specific targets for HCV are an 80% reduction in HCV incidence and a 65% reduction in HCV- related deaths by 2030 (95% and 65%, respectively, for HBV). WHO Global Health Sector Strategy on Viral Hepatitis (2016)

46 46 Global HCV Epidemic is Concentrated Figure 1: Approx. 80% of total viraemic infections lie in a handful of countries. Gower et al. J Hep (2014)

47 Mathematical Model Structure - Demographics Natural

New Births Young (0-19 Years) Male/Female Adult

Recruitment Figure: Demographic structure.

47 47 Mathematical Model Structure - Demographics Natural Death Ageing Young Adult Non-PWID (20-29 Years) Ageing New Births Young (0-19 Years) Male/Female Adult Non-/Ex-PWID (30+ Years) Natural Death PWID Recruitment Figure: Demographic structure. Young Adult PWID (20-29 Years) Ageing Natural & PWID-related Death Natural Death

48 Mathematical Model Structure M/C Risk Exposure To CR High Medical Risk High Community Risk Exposure To MR High Medical Risk Low Community Risk

48 48 Mathematical Model Structure M/C Risk Exposure To CR High Medical Risk High Community Risk Exposure To MR High Medical Risk Low Community Risk Low Medical Risk High Community Risk Exposure To MR Low Medical Risk Low Community Risk Exposure To CR Figure: Medical & community risk structure.

49 49 Mathematical Model Structure Epidemic/Disease Develop HCC (slower if SVR) Spontaneous clearance Spontaneous clearance Spontaneous clearance Spontaneous clearance New Susceptible Susceptible Without Cirrhosis Susceptible Compensated Cirrhosis Progress to DC (slower if SVR) Susceptible Decompensated Cirrhosis Develop HCC Susceptible Hepatocellular Carcinoma Infection Initiate Treatment Treatment Success Treatment Without `" Cirrhosis Treatment Failure Infection Treatment Compensated Cirrhosis Initiate Treatment Treatment Success Treatment Failure Infection DC-related Death DC-related Death Infection HCC-related Death HCC-related Death Chronic HCV Without Cirrhosis Develop Cirrhosis if chronic infection Chronic HCV Compensated Cirrhosis Progress to DC Chronic HCV Decompensated Cirrhosis Develop HCC Chronic HCV Hepatocellular Carcinoma Figure: Epidemic and disease progression structure. Develop HCC

50 50 Cumulative Burden of HCV Infection from 2016 to 2030 Morbidity No. of New Infections No. of New Disease Cases Mortality No. of New Cirrhotic No. of New Decompensated (Advanced) Disease Cases = Total Cirrhosis + Decompensation + HCC. Non- childhood is defined here as 20 years of age and above [ ] million 5.4 [ ] million 3.5 [ ] million 1.3 [ ] million No. of New HCC 560,000 [88,000 1,500,000] No. of Deaths Due to ESLD No. of Deaths Due to Decompensation 1.4 [ ] million 0.9 [ ] million % Of All Deaths 1.3% [ %] % Of All Non- Childhood Deaths 2.1% [ %] No. of Deaths Due to HCC 510,000 [80,000 1,400,000] % Of All Deaths 0.8% [ %] % Of All Non- Childhood Deaths 1.2% [ %]

51 Interventions 51

52 52 Status Quo Treatment (2%,~150,000/yr), Switch to DAAs 1. Reduction of transmission risk (prevention) Reduce all PWID, high medical, and high community risk by 50% Reduce overall transmission risk by 30% Reduce overall transmission risk by 50% 2. Non- targeted treatment at a per capita rate with DAAs Treat 2.0% of chronic infections per year (~150,000 trts/yr) Treat 5.0% of chronic infections per year (~370,000 trts/yr) 3. Combination of the above Reduce overall risk by 50% & treat 5.0% per year (~370,000 trts/yr)

53 53 Overall Chronic HCV Prevalence (%) Impact on Chronic HCV Prevalence Without Intervention From 2016 Reduce High Risk (PWID, Medical & Community) By 50% Reduce Overall Risk By 30% Reduce Overall Risk By 50% Treat 2.0% Annually With DAA (Status Quo) Treat 5.0% Annually With DAA Reduce Overall Risk By 50% & Treat 5.0% Annually With DAA Year

54 54 Total HCV Incidence (per 1000 pyrs) Impact on HCV Incidence Without Intervention From 2016 Reduce High Risk (PWID, Medical & Community) By 50% Reduce Overall Risk By 30% Reduce Overall Risk By 50% Treat 2.0% Annually With DAA (Status Quo) Treat 5.0% Annually With DAA Reduce Overall Risk By 50% & Treat 5.0% Annually With DAA Year

55 55 New Disease Cases (100,000s) Impact on New HCV Disease Cases Without Intervention From 2016 Reduce High Risk (PWID, Medical & Community) By 50% Reduce Overall Risk By 30% Reduce Overall Risk By 50% Treat 2.0% Annually With DAA (Status Quo) Treat 5.0% Annually With DAA Reduce Overall Risk By 50% & Treat 5.0% Annually With DAA Year

56 56 Disease-Related Deaths (100,000s) Impact on HCV-Related Mortality Without Intervention From 2016 Reduce High Risk (PWID, Medical & Community) By 50% Reduce Overall Risk By 30% Reduce Overall Risk By 50% Treat 2.0% Annually With DAA (Status Quo) Treat 5.0% Annually With DAA Reduce Overall Risk By 50% & Treat 5.0% Annually With DAA Year

57 57 Risk Reduction Versus Treatment 1. Reduction of transmission risk (prevention) Reduce all PWID, high medical, and high community risk by 50% Reduce overall transmission risk by 30% Reduce overall transmission risk by 50% 2. Non- targeted treatment at a per capita rate with DAAs Treat 2.0% of chronic infections per year (~150,000 trts/yr) Treat 5.0% of chronic infections per year (~370,000 trts/yr) 3. Combination of the above Reduce overall risk by 50% & treat 5.0% per year (~370,000 trts/yr)

58 58 Total HCV Incidence (per 1000 pyrs) Impact on HCV Incidence Without Intervention From 2016 Reduce High Risk (PWID, Medical & Community) By 50% Reduce Overall Risk By 30% Reduce Overall Risk By 50% Treat 2.0% Annually With DAA (Status Quo) Treat 5.0% Annually With DAA Reduce Overall Risk By 50% & Treat 5.0% Annually With DAA Year

59 59 Disease-Related Deaths (100,000s) Impact on HCV-Related Mortality Without Intervention From 2016 Reduce High Risk (PWID, Medical & Community) By 50% Reduce Overall Risk By 30% Reduce Overall Risk By 50% Treat 2.0% Annually With DAA (Status Quo) Treat 5.0% Annually With DAA Reduce Overall Risk By 50% & Treat 5.0% Annually With DAA Year

60 Achieving WHO Targets 60

61 61 Estimated Treatment Numbers for WHO Targets by 2030* Targeted Intervention Scenarios WHO Target For Incidence And Mortality WHO Target For Incidence Only *WHO targets: 80% reduction in HCV incidence and 65% reduction in HCV- related mortality by 2030 Yearly Number of Treatments Needed

HCV elimination : lessons from Scotland

HCV elimination : lessons from Scotland Sharon Hutchinson Glasgow Caledonian University / Health Protection Scotland BHIVA Hepatology Highlights, Edinburgh, 17 th April 2018 Disclosures Honoraria from